1. Field of the Invention
Chlamydia trachomatis is a major human pathogen responsible for such diseases as trachoma, inclusion conjunctivitis, pneumonia, lymphogranuloma venereum, and mucous membrane genital tract infections such as cervicitis and urethritis. The latter infections may develop systemic complications resulting in epididymitis, salpingitis, or perihepatitis. Thus, it would be of great medical interest to develop reagents and vaccines useful in the diagnosis and treatment of patients infected with Chlamydia trachomatis.
Chlamydia trachomatis species are divided into two biovars, the trachoma biovar and the lymphogranuloma venereum (LGV) biovar, based on the disease inducing characteristics of the species. Each biovar, in turn, includes a number of serovars based on specific serological determinants. The trachoma biovar contains twelve known serovars, while the LGV biovar includes three known serovars. Unique serological determinants which are characteristic of the species, biovar, and serovar have been associated with the major outer membrane protein (MOMP), which protein accounts for over 60% of the total cell wall protein synthesized during chlamydial development. The major outer membrane protein of each serovar appears to have a unique structure and includes species-specific, biovar-specific, and serovar-specific epitopes, allowing Chlamydia trachomatis to be classified by reaction with a panel of monoclonal antibodies specific for the various epitopes. The molecular weight of the various MOMP's generally ranges from about 38 kD to 45 kD. The serovars display varying antigenic complexity, with certain serovars eliciting broad cross-reactivity with others in the same biovar, while other serovars display little or no such cross-reactivity.
Vaccines utilizing purified and unpurified preparations of intact Chlamydia trachomatis have been prepared and tested on monkeys. While successful protection against subsequent challenge with the same chlamydial serovar was achieved, it was found that heterologous serovar challenge resulted in more severe pathology than that experienced by controls who had not been immunized. In human trials, immunization with the vaccines afforded significant protection against the serovar of the vaccine for up to two years, but hypersensitivity resulted from infection with heterologous serovars.
2. Description of the Relevant Art
The nature of the major outer membrane protein and its relation to the biovars and serovars of Chlamydia trachomatis are discussed in Grayston and Wang (1975) J. Infect. Dis. 132:87-105; Stephens et al. (1982) J. Immunol. 128:1083-1089; and Caldwell et al. (1981) Infect. Immun. 31:1161-1176. Inhibition of infectivity of Chlamydia trachomatis by both anti-chlamydial antisera and monoclonal antibodies has been demonstrated. Caldwell and Perry (1982) Infect. Immun. 38:745-754; and Clark et al. (1982) Infect. Immun. 38:1273-1278. Vaccine trials conducted with intact chlamydial elementary bodies are reported by Collier (1961) Lancet 1:795-800; Wang et al. (1967) Amer. J. Ophthal. 63:1615-1630; and Woolridge et al. (1967) Amer. J. Ophthal. 63:1645-1653. The cloning and expression of a gene encoding a 74,000 dalton chlamydial antigen in E. coli is reported by Stephens et al. (1983) Abstracts Annual Meeting American Society of Microbiology, B29, p. 35. Stephens et al. failed to obtain expression of a major outer membrane protein. Wenman and Lovett (1982) Nature 296:68-70, report the expression of a 19,000 dalton Chlamydia trachomatis polypeptide. The polypeptide does not appear to be involved in the major outer membrane protein. Allan et al. (1984) Infect. Immun. 45:637-641, recently reported the cloning of the major outer membrane protein gene. Nano et al. (1985) Infec. Immun. 45:637-641 report the sequencing of the first 25 N-terminal amino acids of the major outer membrane protein and the cloning of at least a portion of the gene. An immunoassay for the detection of Chlamydia trachomatis antigen is described in U.S. Pat. No. 4,497,899.